RESUMO
It is sometimes implied that marsupials are "aplacental," on the presumption that the only mammals that have a placenta are the eponymous "placental" mammals. This misconception has persisted despite the interest in and descriptions of the marsupial placenta, even in Amoroso's definitive chapter. It was also said that marsupials had no maternal recognition of pregnancy and no placental hormone production. In addition, it was thought that genomic imprinting could not exist in marsupials because pregnancy was so short. We now know that none of these ideas have held true with extensive studies over the last four decades definitively showing that they are indeed mammals with a fully functional placenta, and with their own specializations.
Assuntos
Marsupiais , Placentação , Animais , Feminino , Impressão Genômica , Mamíferos , Marsupiais/genética , Placenta , Placentação/genética , GravidezRESUMO
Defensins comprise a family of cysteine-rich antimicrobial peptides with important roles in innate and adaptive immune defense in vertebrates. We characterized alpha and beta defensin genes in three Australian marsupials: the Tasmanian devil (Sarcophilus harrisii), koala (Phascolarctos cinereus), and tammar wallaby (Macropus eugenii) and identified 48, 34, and 39 defensins, respectively. One hundred and twelve have the classical antimicrobial peptides characteristics required for pathogen membrane targeting, including cationic charge (between 1+ and 15+) and a high proportion of hydrophobic residues (>30%). Phylogenetic analysis shows that gene duplication has driven unique and species-specific expansions of devil, koala, and tammar wallaby beta defensins and devil alpha defensins. Defensin genes are arranged in three genomic clusters in marsupials, whereas further duplications and translocations have occurred in eutherians resulting in four and five gene clusters in mice and humans, respectively. Marsupial defensins are generally under purifying selection, particularly residues essential for defensin structural stability. Certain hydrophobic or positively charged sites, predominantly found in the defensin loop, are positively selected, which may have functional significance in defensin-target interaction and membrane insertion.
Assuntos
Anti-Infecciosos/metabolismo , Defensinas/genética , Genoma , Macropodidae/genética , Marsupiais/genética , Phascolarctidae/genética , Seleção Genética/genética , Animais , Austrália , Evolução Molecular , Duplicação Gênica , Genômica , Camundongos , Filogenia , Especificidade da EspécieRESUMO
The first sign of mammalian germ cell sexual differentiation is the initiation of meiosis in females and of mitotic arrest in males. In the mouse, retinoic acid induces ovarian Stra8 expression and entry of germ cells into meiosis. In developing mouse testes, cytochrome P450 family 26, subfamily b, polypeptide 1 (CYP26B1) produced by the Sertoli cells degrades retinoic acid, preventing Stimulated by Retinoic Acid Gene 8 (Stra8), expression and inhibiting meiosis. However, in developing humans, there is no evidence that CYP26B1 acts a meiosis-inhibiting factor. We therefore examined aspects of the retinoic acid/STRA8/CYP26B1 pathway during gonadal development in the tammar wallaby, a marsupial, to understand whether retinoic acid stimulation of STRA8 and CYP26B1 degradation of retinoic acid was conserved between widely divergent mammals. In tammar ovaries, as in human ovaries and unlike the pattern in mice, CYP26B1 expression was not downregulated before the onset of meiosis. Exposure of pre-meiotic tammar ovaries to exogenous retinoic acid in vitro upregulated STRA8 expression compared to controls. We conclude that retinoic acid and STRA8 are conserved factors that control the initiation of meiosis amongst mammals but the role of CYP26B1 as a meiosis-inhibiting factor may be specific to rodents. The identity of the marsupial meiosis-inhibiting factor remains unknown.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Macropodidae/metabolismo , Ácido Retinoico 4 Hidroxilase/metabolismo , Processos de Determinação Sexual/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Meiose , Camundongos , Oogênese/fisiologia , Ácido Retinoico 4 Hidroxilase/genética , Especificidade da Espécie , Espermatogênese/fisiologia , Tretinoína/metabolismoRESUMO
S100 proteins are calcium-binding proteins involved in controlling diverse intracellular and extracellular processes such as cell growth, differentiation, and antimicrobial function. We recently identified a S100-like cDNA from the tammar wallaby (Macropus eugenii) stomach. Phylogentic analysis shows wallaby S100A19 forms a new clade with other marsupial and monotreme S100A19, while this group shows similarity to eutherian S100A7 and S100A15 genes. This is also supported by amino acid and domain comparisons. We show S100A19 is developmentally-regulated in the tammar wallaby gut by demonstrating the gene is expressed in the forestomach of young animals at a time when the diet consists of only milk, but is absent in older animals when the diet is supplemented with herbage. During this transition the forestomach phenotype changes from a gastric stomach into a fermentation sac and intestinal flora changes with diet. We also show that S100A19 is expressed in the mammary gland of the tammar wallaby only during specific stages of lactation; the gene is up-regulated during pregnancy and involution and not expressed during the milk production phase of lactation. Comparison of the tammar wallaby S100A19 protein sequence with S100 protein sequences from eutherian, monotreme and other marsupial species suggest the marsupial S100A19 has two functional EF hand domains, and an extended His tail. An evolutionary analysis of S100 family proteins was carried out to gain a better understanding of the relationship between the S100 family member functions. We propose that S100A19 gene/protein is the ancestor of the eutherian S100A7 gene/protein, which has subsequently modified its original function in eutherians. This modified function may have arisen due to differentiation of evolutionary pressures placed on gut and mammary gland developmental during mammal evolution. The highly regulated differential expression patterns of S100A19 in the tammar wallaby suggests that S100A19 may play a role in gut development, which differs between metatherians and eutherians, and/or include a potential antibacterial role in order to establish the correct flora and protect against spiral bacteria in the immature forestomach. In the mammary gland it may protect the tissue from infection at times of vulnerability during the lactation cycle.
Assuntos
Evolução Molecular , Marsupiais/genética , Filogenia , Isoformas de Proteínas/genética , Proteínas S100/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , DNA Complementar/genética , DNA Complementar/metabolismo , Feminino , Mucosa Gástrica/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Lactação/fisiologia , Macropodidae/classificação , Macropodidae/genética , Macropodidae/metabolismo , Glândulas Mamárias Humanas/crescimento & desenvolvimento , Glândulas Mamárias Humanas/metabolismo , Marsupiais/classificação , Marsupiais/metabolismo , Dados de Sequência Molecular , Gravidez , Isoformas de Proteínas/classificação , Isoformas de Proteínas/metabolismo , Estrutura Terciária de Proteína , Proteínas S100/classificação , Proteínas S100/metabolismo , Análise de Sequência de DNA , Estômago/crescimento & desenvolvimentoRESUMO
Since the discovery in 1968 that dihydrotestosterone (DHT) is a major mediator of androgen action, a convincing body of evidence has accumulated to indicate that the major pathway of DHT formation is the 5α-reduction of circulating testosterone in androgen target tissues. However, we now know that DHT can also be formed in peripheral tissues by the oxidation of 5α-androstane-3α,17ß-diol (adiol). This pathway is responsible for the formation of the male phenotype. We discuss the serendipitous discovery in the tammar wallaby of an alternate pathway by which adiol is formed in the testes, secreted into plasma and converted in peripheral tissues to DHT. This alternate pathway is responsible for virilisation of the urogenital system in this species and is present in the testes at the onset of male puberty of all mammals studied so far. This is the first clear-cut function for steroid 5α-reductase 1 in males. Unexpectedly, the discovery of this pathway in this Australian marsupial has had a major impact in understanding the pathophysiology of aberrant virilisation in female newborns. Overactivity of the alternate pathway appears to explain virilisation in congenital adrenal hyperplasia CAH, in X-linked 46,XY disorders of sex development. It also appears to be important in polycystic ovarian syndrome (PCOS) since PCOS ovaries have enhanced the expression of genes and proteins of the alternate pathway. It is now clear that normal male development in marsupials, rodents and humans requires the action of both the classic and the alternate (backdoor) pathways.
Assuntos
Androgênios , Testosterona , Recém-Nascido , Humanos , Animais , Masculino , Feminino , Androgênios/metabolismo , Austrália , Testosterona/metabolismo , Di-Hidrotestosterona , Macropodidae/metabolismo , VirilismoRESUMO
BACKGROUND: Australian marsupials harbour a diverse array of helminth parasites. Despite current attempts to assess the extent of this diversity in macropodid hosts, it has been suggested that unique parasite fauna of Australian wildlife is difficult to document comprehensively due to the common occurrence of cryptic species. This paper assessed genetic variation within Austrostrongylus thylogale Johnston & Mawson, 1940 from the tammar wallaby, Notamacropus eugenii (Gray), and the quokka, Setonix brachyurus (Quoy & Gaimard), from different localities using the molecular characterisation of the internal transcribed spacers (ITS) within the nuclear ribosomal DNA. METHODS: Thirty-seven specimens of A. thylogale collected from N. eugenii (from Parndana, Kangaroo Island, South Australia, and Perup, Western Australia) and S. brachyurus (from Wellington Dam, Western Australia) were characterised using a molecular-phylogenetic approach utilising the first (ITS1) and second (ITS2) internal transcribed spacers. RESULTS: Genetic variation was detected in both ITS1 and ITS2 between specimens of A. thylogale from N. eugenii and S. brachyurus; however, no variation was detected between specimens collected from N. eugenii from Parndana, South Australia, and Perup, Western Australia. Furthermore, the phylogenetic analyses of ITS sequences showed two clades of A. thylogale originating from two hosts, N. eugenii and S. brachyurus, suggesting the presence of cryptic species. CONCLUSIONS: This study provides evidence of genetic variation within A. thylogale based on collections from two different host species. Morphological studies are required to fully confirm the presence of a new species or cryptic species. Further molecular studies using a larger number of specimens are warranted to explore the genetic variation between A. thylogale from different geographical localities.
Assuntos
Variação Genética , Macropodidae/parasitologia , Nematoides/classificação , Nematoides/genética , Animais , Austrália , DNA de Helmintos/genética , DNA Ribossômico/genética , Especificidade de Hospedeiro , Macropodidae/classificação , Filogenia , Alinhamento de Sequência , TrichostrongyloideaRESUMO
Sex determination and sexual differentiation pathways are highly conserved between marsupials and eutherians. There are 2 different pathways of prostaglandin D2 (PGD2) synthesis: prostaglandin D synthase (PTGDS) and haematopoietic prostaglandin D synthase (HPGDS). PGD2 regulates the subcellular localization of SOX9 during gonadal sexual differentiation. To investigate the function of PGD2 in the tammar gonad, we cultured undifferentiated male gonads in the presence of the HPGDS inhibitor HQL-79 and female gonads with exogenous PGD2 to mimic activation of the PTGDS-PGD2 pathway. Tammar PTGDS and HPGDS have only 50% similarity with mouse and human orthologues, but functional domains are conserved. The expression of SOX9 was unchanged by the treatments in cultured gonads, but its subcellular localization was markedly affected. SOX9 remained cytoplasmic in the Sertoli cells of testes treated with HQL-79. Treated testes developed a thickened ovary-like surface epithelium. In contrast, SOX9 became nuclear in the granulosa cells of developing ovaries treated with PGD2 and the surface epithelium was thin, as in testes. These results demonstrate that PGD2 regulates the subcellular localization of SOX9 and subsequent gonadal development in the developing marsupial gonads, as it does in mice, and that it must have been an ancestral mechanism.
Assuntos
Núcleo Celular/metabolismo , Gônadas/metabolismo , Macropodidae/metabolismo , Prostaglandina D2/metabolismo , Fatores de Transcrição SOX9/metabolismo , Processos de Determinação Sexual , Sequência de Aminoácidos , Animais , Núcleo Celular/efeitos dos fármacos , Sequência Conservada , Feminino , Gônadas/efeitos dos fármacos , Oxirredutases Intramoleculares/química , Oxirredutases Intramoleculares/metabolismo , Lipocalinas/química , Lipocalinas/metabolismo , Masculino , Modelos Biológicos , Ovário/efeitos dos fármacos , Ovário/metabolismo , Piperidinas/farmacologia , Transporte Proteico/efeitos dos fármacos , Fatores de Transcrição SOX9/genética , Processos de Determinação Sexual/efeitos dos fármacos , Diferenciação Sexual/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismoRESUMO
Background: Most animal studies of spinal cord injury are conducted in quadrupeds, usually rodents. It is unclear to what extent functional results from such studies can be translated to bipedal species such as humans because bipedal and quadrupedal locomotion involve very different patterns of spinal control of muscle coordination. Bipedalism requires upright trunk stability and coordinated postural muscle control; it has been suggested that peripheral sensory input is less important in humans than quadrupeds for recovery of locomotion following spinal injury. Methods: We used an Australian macropod marsupial, the tammar wallaby (Macropuseugenii), because tammars exhibit an upright trunk posture, human-like alternating hindlimb movement when swimming and bipedal over-ground locomotion. Regulation of their muscle movements is more similar to humans than quadrupeds. At different postnatal (P) days (P7-60) tammars received a complete mid-thoracic spinal cord transection. Morphological repair, as well as functional use of hind limbs, was studied up to the time of their pouch exit. Results: Growth of axons across the lesion restored supraspinal innervation in animals injured up to 3 weeks of age but not in animals injured after 6 weeks of age. At initial pouch exit (P180), the young injured at P7-21 were able to hop on their hind limbs similar to age-matched controls and to swim albeit with a different stroke. Those animals injured at P40-45 appeared to be incapable of normal use of hind limbs even while still in the pouch. Conclusions: Data indicate that the characteristic over-ground locomotion of tammars provides a model in which regrowth of supraspinal connections across the site of injury can be studied in a bipedal animal. Forelimb weight-bearing motion and peripheral sensory input appear not to compensate for lack of hindlimb control, as occurs in quadrupeds. Tammars may be a more appropriate model for studies of therapeutic interventions relevant to humans.
RESUMO
Many developmental functions in marsupials and eutherian mammals are accomplished by different tissues, but similar genes.
Assuntos
Eutérios/genética , Eutérios/fisiologia , Animais , Eutérios/crescimento & desenvolvimento , Evolução Molecular , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Lactação/fisiologia , Mamíferos/fisiologia , Glândulas Mamárias Humanas/fisiologia , Marsupiais/fisiologia , Placentação/fisiologia , GravidezRESUMO
Eutherians are often mistakenly termed 'placental mammals', but marsupials also have a placenta to mediate early embryonic development. Lactation is necessary for both infant and fetal development in eutherians and marsupials, although marsupials have a far more complex milk repertoire that facilitates morphogenesis of developmentally immature young. In this study, we demonstrate that the anatomically simple tammar placenta expresses a dynamic molecular program that is reminiscent of eutherian placentation, including both fetal and maternal signals. Further, we provide evidence that genes facilitating fetal development and nutrient transport display convergent co-option by placental and mammary gland cell types to optimize offspring success.
Assuntos
Eutérios/genética , Lactação/genética , Placentação/genética , Animais , Evolução Biológica , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Glândulas Mamárias Animais/metabolismo , Camundongos , Leite , Placenta/metabolismo , GravidezRESUMO
When 60-day-old tammar wallaby pouch young (Macropus eugenii) are fostered to mothers at 120 days of lactation, their growth, developmental rate and maturation of their GH/IGF axes are markedly accelerated. To determine the effect of fostering on energy intake, body composition and fat accretion, we first measured total body fat and lean mass in these young. Next, we mimicked the triglyceride oleic and palmitic acid composition of 120-day milk by supplementing 60 day young with these fatty acids and comparing their growth with that of growth accelerated young. There was no difference in the weight or growth axis maturation of supplemented young but there was significantly more body fat in these and in the growth-accelerated fostered young than in controls. We conclude that the accelerated growth and GH/IGF axis maturation observed previously in fostered young is most likely due to increased milk consumption and earlier access to specific nutrients.
Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Composição Corporal , Macropodidae/crescimento & desenvolvimento , Macropodidae/fisiologia , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Tecido Adiposo/anatomia & histologia , Tecido Adiposo/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Composição Corporal/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Suplementos Nutricionais , Metabolismo Energético/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hormônio do Crescimento/sangue , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Lactação/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Macropodidae/sangue , Macropodidae/genética , Leite/metabolismo , Óleos/farmacologia , Tamanho do Órgão/efeitos dos fármacos , Período Pós-Parto/sangue , Período Pós-Parto/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Recent studies using the mouse showed an inverse correlation between the Caveolin 1 gene expression and lactation, and this was regulated by prolactin. However, current study using mammary explants from pregnant mice showed that while insulin (I), cortisol (F) and prolactin (P) resulted in maximum induction of the ß-casein gene, FP and IFP resulted in the downregulation of Caveolin 1. Additionally, IF, FP and IFP resulted in the downregulation of Caveolin 2. Immunohistochemistry confirmed localisation of Caveolin 1 specific to myoepithelial cells and adipocytes. Comparative studies with the tammar wallaby showed Caveolin 1 and 2 had 70-80% homology with the mouse proteins. However, in contrast to the mouse, Caveolin 1 and 2 genes showed a significantly increased level of expression in the mammary gland during lactation. The regulation of tammar Caveolin 1 and 2 gene expression was examined in mammary explants from pregnant tammars, and no significant difference was observed either in the absence or in the presence of IFP.
Assuntos
Caveolina 1/genética , Caveolina 2/genética , Macropodidae/genética , Glândulas Mamárias Animais/metabolismo , Adipócitos/metabolismo , Sequência de Aminoácidos , Animais , Caseínas/genética , Regulação para Baixo/genética , Células Epiteliais/metabolismo , Feminino , Expressão Gênica/genética , Hormônios/genética , Hidrocortisona/genética , Insulina/genética , Lactação/genética , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Gravidez , Prolactina/genética , Homologia de Sequência de AminoácidosRESUMO
Marsupial joeys are born ectothermic and develop endothermy within their mother's thermally stable pouch. We hypothesized that Tammar wallaby joeys would switch from α-stat to pH-stat regulation during the transition from ectothermy to endothermy. To address this, we compared ventilation (Ve), metabolic rate (Vo2), and variables relevant to blood gas and acid-base regulation and oxygen transport including the ventilatory requirements (Ve/Vo2 and Ve/Vco2), partial pressures of oxygen (PaO2), carbon dioxide (PaCO2), pHa, and oxygen content (CaO2) during progressive hypothermia in ecto- and endothermic Tammar wallabies. We also measured the same variables in the well-studied endotherm, the Sprague-Dawley rat. Hypothermia was induced in unrestrained, unanesthetized joeys and rats by progressively dropping the ambient temperature (Ta). Rats were additionally exposed to helox (80% helium, 20% oxygen) to facilitate heat loss. Respiratory, metabolic, and blood-gas variables were measured over a large body temperature (Tb) range (â¼15-16°C in both species). Ectothermic joeys displayed limited thermogenic ability during cooling: after an initial plateau, Vo2 decreased with the progressive drop in Tb. The Tb of endothermic joeys and rats fell despite Vo2 nearly doubling with the initiation of cold stress. In all three groups the changes in Vo2 were met by changes in Ve, resulting in constant Ve/Vo2 and Ve/Vco2, blood gases, and pHa. Thus, although thermogenic capability was nearly absent in ectothermic joeys, blood acid-base regulation was similar to endothermic joeys and rats. This suggests that unlike some reptiles, unanesthetized mammals protect arterial blood pH with changing Tb, irrespective of their thermogenic ability and/or stage of development.